Background
Acute gastroenteritis is a common cause of morbidity and mortality worldwide. Conservative estimates put diarrhea in the top 5 causes of deaths worldwide, with most occurring in young children in nonindustrialized countries. In industrialized countries, diarrheal diseases are a significant cause for morbidity across all age groups. Etiologies include bacteria, viruses, parasites, toxins, and drugs. Viruses are responsible for a significant percentage of cases affecting patients of all ages; in the United States, viruses are the leading cause of acute gastroenteritis. [1] Viral gastroenteritis ranges from a self-limited watery diarrheal illness (usually <1 wk) associated with symptoms of nausea, vomiting, anorexia, malaise, or fever, to severe dehydration resulting in hospitalization or even death.
The clinician encounters acute viral gastroenteritis in 3 settings. The first is sporadic gastroenteritis in infants, which most frequently is caused by rotavirus. [2] The second is epidemic gastroenteritis, which occurs either in semiclosed communities (eg, families, institutions, ships, vacation spots) or as a result of classic food-borne or water-borne pathogens. [3] Most of these infections are caused by caliciviruses. The third is sporadic acute gastroenteritis of adults, which most likely is caused by caliciviruses, rotaviruses, astroviruses, or adenoviruses.
For patient education resources, see Digestive Disorders Center, as well as Gastroenteritis (Stomach Flu), Norovirus Infection, and Diarrhea.
Pathophysiology
Viral spread from person to person occurs by fecal-oral transmission of contaminated food and water. Some viruses, like noroviruses, may be transmitted by an airborne route. Clinical manifestations are related to intestinal infection, but the exact mechanism of the induction of diarrhea is not clear.
The most extensive studies have been done with rotavirus. Rotaviruses attach and enter mature enterocytes at the tips of small intestinal villi. They cause structural changes to the small bowel mucosa, including villus shortening and mononuclear inflammatory infiltrate in the lamina propria.
The current knowledge on the mechanisms leading to diarrheal disease by rotavirus is as follows: [4]
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Rotavirus infections induce maldigestion of carbohydrates, and their accumulation in the intestinal lumen, as well as a malabsorption of nutrients and a concomitant inhibition of water reabsorption, can lead to a malabsorption component of diarrhea.
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Rotavirus secretes an enterotoxin, NSP4, which leads to a Ca2+ -dependent Cl- secretory mechanism. Mobilization of intracellular calcium associated with NSP4 expressed endogenously or added exogenously is known to induce transient chloride secretion.
Morphologic abnormalities can be minimal, and studies demonstrate that rotavirus can be released from infected epithelial cells without destroying them. Viral attachment and entry into the epithelial cell without cell death may be enough to initiate diarrhea. The epithelial cell synthesizes and secretes numerous cytokines and chemokines, which can direct the host immune response and potentially regulate cell morphology and function. Studies also suggest that one of the nonstructural viral proteins may act as an enterotoxin, promoting active chloride secretion mediated through increases in intracellular calcium concentration. Toxin-mediated diarrhea would explain the observation that villus injury is not necessarily linked to diarrhea.
Etiology
Sporadic infantile viral gastroenteritis
Group A rotavirus causes 25-65% of severe infantile gastroenteritis worldwide. Acute infections with group C are quite frequent in the United States and worldwide.
After rotavirus, the most important cause of acute infantile gastroenteritis probably is calicivirus infection. Seroepidemiologic studies have shown that antibodies to caliciviruses are present in 50-90% of children younger than 2 years in Kuwait, Italy, Kenya, China, London, and South Africa. Using broadly reactive reverse-transcription polymerase chain reaction for calicivirus to study stool specimens from children with acute gastroenteritis, studies have found these viruses in 7-22% of cases.
Astrovirus infection is associated with 2-9% of cases of infantile gastroenteritis worldwide, making it the third most frequent cause after rotavirus and calicivirus. The burden of astrovirus disease in developing countries might be especially high. In a study comprising pediatric data from 82,082 children in 8 countries, using 25,898 surveillance stools and 7,077 diarrheal stools, investigators found 35% of children had astrovirus infections, with an astrovirus prevalence of 5.6% in diarrheal stools. [5] Children with astrovirus infection were 2.3 times more likely to experience diarrhea, with undernutrition a risk factor. [5]
Researchers have recognized for a long time that certain enteric adenoviruses are an important cause of infantile gastroenteritis. Studies confirm that they cause 2-6% of cases.
A study by Chhabra et al indicated that in addition to rotavirus and norovirus, frequent causes of acute gastroenteritis in US children include adenovirus, sapovirus, and astrovirus. The study, which included patients from hospitals, emergency departments, and primary care clinics in three US counties, found that stool specimens from 22.1% of children under age 5 years who presented with acute gastroenteritis and who tested negative for rotavirus and norovirus, tested positive for adenovirus (11.8%), sapovirus (5.4%), and astrovirus (4.9%). [6]
Epidemic viral gastroenteritis
Most cases of epidemic viral gastroenteritis in adults and children are caused by the caliciviruses. Some examples include Norovirus (formerly called Norwalk-like viruses), genogroup I (eg, Norwalk, Southampton, Desert Shield, Cruise Ship); norovirus, genogroup II (eg, Snow Mountain, Mexico, White River, Lordsdale, Bristol, Camberwell, Toronto, Hawaii, Melksham); and sapovirus (formerly Sapporo-like viruses), which sometimes are referred to as genogroup III, although they are not like Norwalk (eg, Sapporo, Parkville, Manchester, Houston, London).
Modern molecular diagnostic techniques, such as broadly reactive reverse-transcription polymerase chain reaction, have linked these viruses to epidemics associated with oysters, contaminated community water supplies, restaurant food, hospital patients and staff, day care facilities, nursing homes, college dormitories, military ships, cruise ships, and vacation spots. Rotavirus and astrovirus also may cause epidemics of viral gastroenteritis.
Sporadic adult viral gastroenteritis
Few studies have examined the causes of sporadic cases of adult viral gastroenteritis. Seroepidemiologic evidence suggests that the etiologies are (in descending order of frequency) caliciviruses, non–group A rotavirus, astrovirus, and adenovirus.
Epidemiology
United States data
Before the advent of rotavirus vaccine, more than 3.5 million infants developed acute viral gastroenteritis, resulting in more than 500,000 office visits, 55,000 hospitalizations, and 30 deaths. [7, 8] However, a CDC study by Tate et al demonstrated a decline in the seasonality of rotavirus following the 2006 introduction of the rotavirus vaccine. [9]
The investigators evaluated data for July 2000 through June 2008 to assess national, regional, and local trends in rotavirus testing and detection and found not only was the onset of the 2007-2008 rotavirus season delayed 15 weeks and the peak delayed 8 weeks relative to the prevaccine rotavirus season from 2000 to 2006, but the 2007-2008 season also lasted a little over half (14 wk) of the median prevaccine seasons (26 weeks). [9] Moreover, there was a 67% decline in the number and a 69% decline in the proportion of 2007-2008 rotavirus-positive test results compared with the median in 2000-2006.
Rotavirus is the most common etiologic agent of health care–acquired diarrhea in pediatric patients. [10] Community- and health care–acquired infections have similar temporal distributions; they are caused by the same viral subtypes; and they affect children of the same age groups. All of the health care–acquired infections with known viral subtypes occurred while the same subtype was still active in the community, suggesting that health care–acquired infections arise from repeated introduction of the community-acquired rotavirus into the hospital setting. [11]
Statistics on sporadic cases of adult viral gastroenteritis are not known; however, food- and water-borne epidemics of viral gastroenteritis are monitored by the US Centers for Disease Control and Prevention (CDC) surveillance programs.
Norovirus causes an annual 19-21 million cases of acute gastroenteritis occur in the United States, resulting in 1.7-1.9 million outpatient visits and 400,000 emergency department visits, primarily in young children. [12] It is the leading cause of gastroenteritis outbreaks and contributes to an estimated 56,000-71,000 hospitalizations and 570-800 deaths, mainly affecting children and the elderly. [12] The CDC estimates that norovirus alone causes nearly 5.5 million cases of food-related illness each year (of a total of 48 million cases from all causes). [13] The genus Norovirus, formerly called the Norwalk-like virus, is a member of the family Caliciviridae.
Noroviruses are now recognized to be a common cause of gastroenteritis in new settings, including nursing homes and other healthcare settings, cruise ships, in other travelers, and in immunocompromised patients. [14] In 2010-2011, norovirus was transmitted among players and staff of the National Basketball Association. [15]
In March 2012, the CDC reported a rise in foodborne disease outbreaks caused by imported food in 2009 and 2011. Nearly 50% of the outbreaks implicated food that was imported from regions not previously associated with outbreaks (mostly fish and peppers). Approximately 45% percent of the imported foods causing outbreaks came from Asia. [16]
In 2015, the CDC published its first National Outbreak Reporting System (NORS) results on data on acute gastroenteritis outbreaks spread through person-to-person contact, environmental contamination, and unknown modes of transmission in all 50 US states, the District of Columbia (DC), and Puerto Rico between 2009 and 2013. [17] The following were among the NORS findings:
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A total of 10,756 outbreaks of acute gastroenteritis over the study period resulted in 356,532 reported illnesses, 5,394 hospitalizations, and 459 deaths.
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In any given year, there was an increase in the median outbreak reporting rate for all sites, from 2.7 outbreaks per million population in 2009 to 11.8 outbreaks in 2013, with almost one third (31%) of these outbreaks having an unknown cause, whereas of the outbreaks with a suspected or confirmed cause, norovirus was reported in 84%.
The frequency is seasonal. Acute gastroenteritis outbreaks most frequently occurring during the winter (December-February). [17] The highest incidence of rotavirus cases occurs during the months from November to April. Cruise ship outbreaks of noroviruses are more common during the summer months. [10]
International data
Acute viral gastroenteritis is a leading cause of infant mortality throughout the world. By age 3 years, virtually all children become infected with the most common agents. Rotavirus causes 2 million hospitalizations and 600,000-875,000 deaths per year.
Globally, Norovirus causes an estimated 20% of cases of acute gastroenteritis and is considered the most common of this condition (most common strain: genogroup II genotype 4 [18] ). [10] It is responsible for 685 million cases annually, with 200 million cases involving children younger than 5 years and resulting in an estimated 50,000 child deaths every year, primarily in developing countries. [10]
The occurrence of noroviruses on cruise ships has led to the use of the term "the cruise ship virus" as another name for these viruses. Some illnesses previously attributed to sea sickness are now recognized to be caused by norovirus infections. [14]
Age-related demographics
Acute viral gastroenteritis occurs throughout life. Severe cases are seen in the very young and in the elderly. [19] The etiology also varies with age. In infants, most cases are due to rotavirus; in adults, the most common cause is norovirus.
Prognosis
Acute viral gastroenteritis is generally self-limited and has a good prognosis. [1]
Morbidity/mortality
Severe cases are seen in the elderly, infant, and immunosuppressed populations, including transplant patients. [1]
Rotavirus infantile gastroenteritis is an important cause of infant mortality in the developing world.
In the United States, elderly persons have the highest risk of death from gastroenteritis.
Caliciviruses may kill more people in the United States than do rotaviruses.
Noroviruses are the most common cause of gastroenteritis in nursing homes, and several such outbreaks have resulted in deaths due to aspiration or exacerbation of another chronic disease. Norovirus infections in hospitalized patients are more severe than those seen in otherwise healthy persons. [14]
In a 2012 report, the CDC revealed enteritis deaths more than doubled in the United States, an increase to 17,000 in 2007 from about 7,000 in 1999. [20] Adults over 65 years old accounted for 83% of deaths. Clostridium difficile (C difficile) and norovirus were the most common infectious causes of gastroenteritis-associated deaths. Norovirus was associated with about 800 deaths annually, although there were 50% more deaths in years when epidemics were caused by new strains of the virus. [20] New norovirus strains continue to emerge. [18, 21, 22]
